We sought S-100 protein in sections prepared from formalin-fixed paraffin-embedded tumor and normal tissues by an immunoperoxidase technique with a rabbit anti-bovine S-100 protein antiserum as first antibody and aminoethyl carbazole as developer. S-100 protein was demonstrated in 56 of 56 cutaneous melanomas, regardless of their primary or metastatic status, and in 35 of 35 nevocytic nevi. The amount of S-100 protein was independent of the degree of melanization of the tumors. Only 1 of 51 non-neural non-melanocytic tumors tested contained S-100 protein. The technique is valuable in confirming the melanocytic nature of primary or metastatic tumors and in detecting small foci of metastatic melanoma in lymph nodes and other tissues. It also seems applicable to research on melanocytic anomalies.